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RATIONALE While children with primary ciliary dyskinesia (PCD) typically have low nasal nitric oxide (nNO), some children with indisputable PCD may have unexplained high nNO levels. OBJECTIVES To look for relationships between nNO measures and genetic findings (and cilia motility or ultrastructure when available) in PCD children with a known genotype. METHODS We studied retrospectively 73 PCD children (median (range) age 9.5 (2.1 to 18.2) years). nNO was the mean value of a plateau reached while velum was closed (nNO-VC, threshold 77 nL.min-1), or calculated as the average of 5 peaks obtained during tidal breathing (nNO-TB, threshold 40 nL.min-1). Cilia beat was classified either as motile (including dyskinetic pattern) or immotile depending on whether motility was present or absent in all cilia, or as a mixture of motile and immotile cilia. Genotypes were classified as: pathogenic mutations in a gene known to be associated with high nNO (mild genotype); bi-allelic truncating mutations in other genes (severe mutations); putative hypomorphic pathogenic mutation (missense, single amino-acid deletion or moderate splicing mutations) in at least one allele thought to be possibly associated with a residual production of a functional protein. RESULTS nNO was above the discriminant threshold in 16/73 (21.9%) children (11 nNO-VC and 5 nNO-TB). High nNO was less frequent in children with severe mutations (2/42) than in those with mild genotypes (7/10) or at least one hypomorphic mutation (7/21)(P < 0.0001). Median [IQR] nNO-VC values (n=60) were significantly different in the three genotypic groups: severe mutations 18 [10;26] nL.min-1 (n=36), possible residual functional protein production (putative hypomorphic mutations) 23 [16;68] nL.min-1 (n=17), and mild genotypes 139 [57;216] nL.min-1 (n=7); P=0.0002. The higher the cilia motility the higher the nNO-VC (16 [10;23], 23 [17;56], and 78 [45;93] nL.min-1 in patients with respectively immotile, dyskinetic motile/immotile, and dyskinetic motile cilia; P<0.0001), while nNO values were scattered across different ultrastructure defects (P = 0.07). CONCLUSIONS In PCD children, high nNO values were linked not only to specific genes and but also to potentially hypomorphic mutations in other genes (with possible functional protein production). nNO values increased with the proportion of motile cilia.